New insights on triggering muscle formation
"In adult skeletal muscle, the process of generating muscle -- myogenesis -- depends on activating MuSCs that are in a resting, or quiescent, state. As we age, our MuSCs transition to a permanently inactive state called senescence, from which they can't be 'woken up' to form new muscle fibers," says Lorenzo Puri, M.D., Ph.D., professor in the Development, Aging and Regeneration Program at SBP. "If we could encourage senescent MuSCs to start replicating and advance through myogenesis -- perhaps through pharmacological interventions -- we may have a way to help build muscle in patients that need it," adds Puri. The goal of the study was to define the molecular determinants that lead to irreversible MuSC senescence. Using a combination of a mouse model and human fibroblasts, the team found that the reason old MuSCs can't be activated to generate muscle cells is that they spontaneously activate a DNA damage response (DDR) even in the absence of exp...